Rare Case of a Cutaneous Fingertip Schwannoma: A Case Report and Review of Literature.

Background: Soft tissue masses of the hand are common and mostly benign, including ganglion cysts, glomus tumors, lipomas, and giant cell tumors of the tendon sheath. Schwannomas are benign nerve sheath tumors but are rarely found on the distal parts of the digits. The authors present a case of a schwannoma located at the tip of the finger. Methods: An otherwise healthy 26-year-old man presented because of a 10-year history of a slowly growing mass on the tip of his right little finger that significantly interfered with his right hand function. The patient underwent hand radiographs and surgical excision of the tumor. Results: Pathologic evaluation determined that the mass was a schwannoma with positive immunohistochemistry for S-100 and SOX-10. The patient reported complete resolution of symptoms associated with the tumor and his satisfaction with the surgical outcome. Conclusions: Imaging studies, such as radiographs, ultrasound, and magnetic resonance imaging, are critical in the diagnostic workup of soft tissue masses of the hand to better understand involvement of the tumor to musculature, vasculature, and other pertinent bony structures. Although quite common, schwannomas may be hard to differentiate from other soft tissue tumors, and a review of the literature demonstrates the importance of providers utilizing imaging and other diagnostics before proceeding to treatment.

Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars.

Although oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells could escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors in escape from OIS and identify senescence-associated chromatin scars (SACSs) as an epigenetic memory of OIS detectable during colorectal cancer progression. POU2F2 levels are already elevated in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape necessary for senescence escape and reveal POU2F2 and SACS gene signatures as valuable biomarkers with diagnostic and prognostic potential.

Autoimmune Hepatitis Induced after Treatment of Syphilitic Hepatitis.

We present a unique case of biopsy-proven syphilitic hepatitis which presented as severe acute liver injury with significant elevation in aminotransferases and bilirubin, and improved with antibiotic therapy. However, the patient returned weeks after initial presentation with new-onset acute liver injury and had developed hypergammaglobulinemia, positive autoantibody titers, and repeat liver biopsy demonstrating interface hepatitis, supporting a diagnosis of autoimmune hepatitis. He had an otherwise unrevealing etiologic workup, and responded to glucocorticoid therapy. We believe that syphilitic hepatitis and its treatment subsequently triggered an immunogenic response, leading to autoimmune hepatitis. Autoimmune hepatitis is a chronic liver disease thought to manifest as a result of predisposing genetic factors in combination with environmental insults, especially hepatotropic pathogens. Syphilis is a sexually transmitted disease caused by Treponema pallidum that has been associated with autoimmunity and the development of autoantibodies. We propose that in the setting of syphilitic hepatitis, a molecular mimicry event resulting from structural similarities between T. pallidum and liver antigens, as well as impaired regulatory T-cell function, led to the breakdown of immune tolerance and the onset of autoimmune hepatitis. To support this hypothesis, further molecular analyses and case series are necessary to determine if syphilitic hepatitis and its treatment are risk factors for the onset of autoimmune hepatitis. Autoimmune hepatitis should be considered early as the cause of acute liver injury in susceptible patients with risk factors for the disease, as prompt recognition and appropriate treatment may prevent progression of liver injury and result in improved outcomes.

Disease Control Achieved Using Atezolizumab + Bevacizumab in a Patient With Sarcomatoid Hepatocellular Carcinoma (SHCC), a Rare Variant Excluded From the IMbrave150 Trial.

Sarcomatoid hepatocellular carcinoma (SHCC) is a rare variant of liver cancer that lacks treatment options. The IMbrave trail demonstrated the efficacy of atezolizumab and bevacizumab (A + B) in patients with unresectable hepatocellular carcinoma but excluded patients with sarcomatoid variants. Herein, we describe a case of disease control achieved using the IMbrave regimen in a patient with sarcomatoid hepatocellular carcinoma.

Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.

Quantitative characterization of human breast tissue based on deep learning segmentation of 3D optical coherence tomography images.

In this study, we performed dual-modality optical coherence tomography (OCT) characterization (volumetric OCT imaging and quantitative optical coherence elastography) on human breast tissue specimens. We trained and validated a U-Net for automatic image segmentation. Our results demonstrated that U-Net segmentation can be used to assist clinical diagnosis for breast cancer, and is a powerful enabling tool to advance our understanding of the characteristics for breast tissue. Based on the results obtained from U-Net segmentation of 3D OCT images, we demonstrated significant morphological heterogeneity in small breast specimens acquired through diagnostic biopsy. We also found that breast specimens affected by different pathologies had different structural characteristics. By correlating U-Net analysis of structural OCT images with mechanical measurement provided by quantitative optical coherence elastography, we showed that the change of mechanical properties in breast tissue is not directly due to the change in the amount of dense or porous tissue.

Acute Liver Injury as a Manifestation of Secondary Syphilis.

In the United States, the incidence of new cases of syphilis has been rising. The number of cases of primary and secondary syphilis has continued to increase almost every year over the past 2 decades. Secondary syphilis has a variety of clinical manifestations. A frequently overlooked presentation is that of syphilitic hepatitis, which should be part of the differential diagnosis for patients with elevated liver enzymes, a maculopapular rash, and/or risk factors for contracting syphilis. In this study, we report a rare and unusual case of a man with a remote history of syphilis infection who developed acute liver injury.

Critical role of interferons in gastrointestinal injury repair.

The etiology of ulcerative colitis is poorly understood and is likely to involve perturbation of the complex interactions between the mucosal immune system and the commensal bacteria of the gut, with cytokines acting as important cross-regulators. Here we use IFN receptor-deficient mice in a dextran sulfate sodium (DSS) model of acute intestinal injury to study the contributions of type I and III interferons (IFN) to the initiation, progression and resolution of acute colitis. We find that mice lacking both types of IFN receptors exhibit enhanced barrier destruction, extensive loss of goblet cells and diminished proliferation of epithelial cells in the colon following DSS-induced damage. Impaired mucosal healing in double IFN receptor-deficient mice is driven by decreased amphiregulin expression, which IFN signaling can up-regulate in either the epithelial or hematopoietic compartment. Together, these data underscore the pleiotropic functions of IFNs and demonstrate that these critical antiviral cytokines also support epithelial regeneration following acute colonic injury.

Infectious Mononucleosis Causing Acute Liver Failure and Hemolytic Anemia in a Patient with Underlying Hereditary Hemochromatosis.

Infectious mononucleosis is a largely benign disease process that occurs secondary to infection with the Epstein-Barr virus. However, it can also present with more serious complications, including auto-immune hemolytic anemia and acute liver failure. Hereditary hemochromatosis is a genetic disorder that leads to organ damage via increased iron uptake and deposition. This case report describes a 25-year-old man who presented with acute liver failure and severe hemolytic anemia. Workup revealed that not only did he have a rare presentation of Epstein-Barr virus-induced acute liver failure and C3-positive IgG-negative hemolytic anemia, he also had previously undiagnosed hereditary hemochromatosis. This combined presentation of these pathologies presents a unique opportunity to study their interaction and possible synergistic pathophysiology. Furthermore, the evolving understanding of the disease mechanisms behind these disease processes is described.

Acute Liver Injury due to Severe Epstein-Barr Virus Infection.

Epstein-Barr virus (EBV) is a widely dispersed herpesvirus, transferred through close personal contact between susceptible individuals and asymptomatic shedders of the virus. The liver is often affected, and involvement is usually subclinical and self-limited. However, immunocompromised patients and, more rarely, immunocompetent individuals can develop a severe and potentially fatal acute liver injury. To differentiate EBV hepatitis from other conditions, such as autoimmune hepatitis, lymphoproliferative disorders, and drug-induced liver injury, correlation with clinical history, laboratory findings, and histopathologic features is crucial. We report a unique case of a man who developed acute liver injury from a severe EBV infection.

Concurrent Langerhans Cell Histiocytosis and Autoimmune Hepatitis: A Case and Review of the Literature.

Autoimmune hepatitis (AIH) and Langerhans cell histiocytosis (LCH) are two independently rare disease processes that can have similar presentations. We present a unique, complex case that required a multidisciplinary approach to ultimately diagnose and treat the patient. A 20-year-old male with no significant history presented with worsening jaundice, diffuse, pruritic rash, and abdominal pain over one month. On admission, the patient's labs showed significantly elevated liver function tests (LFTs), eosinophilia, and anemia. The exam was notable for diffuse lymphadenopathy (LAD), hepatosplenomegaly, and a diffuse, non-blanching, morbilliform rash. Interdisciplinary workup was notable for positive anti-smooth muscle antibody (ASMA) and anti-neutrophilic antibody (ANA). A liver biopsy showed severe inflammation with interface activity, consistent with AIH. A lymph node (LN) biopsy showed findings consistent with LCH, including histiocyte clusters. He was started on high-dose steroids with LAD/LFT improvement; yet, his course was complicated by a gastrointestinal (GI) bleed requiring a hemicolectomy. The patient was transferred to a larger referral center where he continued to improve with steroids and was ultimately discharged. This case was notable for an LN biopsy showing histiocyte clusters with reniform nuclei, nuclear grooves, and eosinophils with immunohistochemical stains positive for S-100, CD1a, fascin, langerin, CD45, and CD68, consistent with LCH. The resected colon showed atypical histiocyte proliferation positive for fascin, CD4, and CD68. Other findings, including elevated LFTs, ASMA, and a liver biopsy showing inflammation with interface activity, eosinophils, plasma cells, and characteristic fibrosis, supported a diagnosis of AIH. In either case, steroids were indicated.

A Case Report of Alloimmune Hepatitis after Direct-acting Antiviral Treatment in a Liver Transplant Patient.

Direct-acting antiviral (DAA) therapy is often well-tolerated, and adverse events from DAA therapy are uncommon. We report a case of a woman who underwent orthotopic liver transplant for chronic hepatitis C infection and later developed alloimmune hepatitis shortly after starting DAA therapy for recurrent hepatitis C infection. The patient developed acute alloimmune hepatitis approximately 2 weeks after starting treatment with sofosbuvir, velpatasvir, and voxilaprevir. This case report proposes a dysregulation of immune surveillance due to the DAA stimulation of host immunity and rapid elimination of hepatitis C viral load as a precipitating factor for the alloimmune process, leading to alloimmune hepatitis in a post-transplant patient who starts on DAA.

Acute Liver Injury in a Patient Treated With Rosuvastatin: A Rare Adverse Effect.

Drug-induced liver injury (DILI) is among the challenging liver conditions encountered by clinicians today. It has a low incidence in the general population with an approximated annual incidence of 10 - 15 cases per 10,000 - 100,000 persons who have taken prescription medications. Nevertheless, DILI remains the most frequent cause of acute liver injury in the United States. Rosuvastatin is a commonly prescribed medication that, similar to other statins, is associated with serum aminotransferase elevations that are mild, asymptomatic and usually self-limited. Here, we report a case of a man who developed acute liver injury after taking rosuvastatin for hypercholesterolemia treatment. Moreover, DILI with autoimmune features represents a key subgroup of hepatotoxicity attributable to medication exposure. Similar to idiopathic autoimmune hepatitis, circulating autoantibodies and a hypergammaglobulinemia are often present in the serum of such individuals. However, such findings are not invariable. In the case reported here, these laboratory features were absent, but a liver biopsy demonstrated interface hepatitis with a prominent plasma cell infiltrate, histologic components consistent with an immune-mediated drug reaction. After withdrawal of the offending medication did not result in complete resolution, corticosteroid therapy was administered with a subsequent clinical response, confirming the diagnosis.

Malignant Granular Cell Tumor of the Bile Duct.

A 56-year-old man presented to the emergency department with painless jaundice and weight loss. Abdominal ultrasound detected dilation of the common bile duct and the intrahepatic bile ducts. Follow-up with endoscopic retrograde cholangiography exposed a stricture of the common hepatic duct, with cholangioscopy identifying an infiltrating tumor. Biopsy revealed a granular cell tumor, which was confirmed by positive S-100 immunohistochemical staining. Surgical excision confirmed granular cell tumor of the bile duct with morphological features suggestive of malignancy.

Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer.

INTRODUCTION: At least four major categories of invasive breast cancer that are associated with different clinical outcomes have been identified by gene expression profiling: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) and basal-like. However, the prevalence of these phenotypes among cases of ductal carcinoma in situ (DCIS) has not been previously evaluated in detail. The purpose of this study was to compare the prevalence of these distinct molecular subtypes among cases of DCIS and invasive breast cancer. METHODS: We constructed tissue microarrays (TMAs) from breast cancers that developed in 2897 women enrolled in the Nurses' Health Study (1976 to 1996). TMA slides were immunostained for oestrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor (EGFR). Using these immunostain results, cases were grouped into molecularly defined subtypes. RESULTS: The prevalence of the distinct molecular phenotypes differed significantly between DCIS (n = 272) and invasive breast cancers (n = 2249). The luminal A phenotype was significantly more frequent among invasive cancers (73.4%) than among DCIS lesions (62.5%) (p = 0.0002). In contrast, luminal B and HER2 molecular phenotypes were both more frequent among DCIS (13.2% and 13.6%, respectively) as compared with invasive tumours (5.2% and 5.7%, respectively) (p < 0.0001). The basal-like phenotype was more frequent among the invasive cancers (10.9%) than DCIS (7.7%), although this difference was not statistically significant (p = 0.15). High-grade DCIS and invasive tumours were more likely to be HER2 type and basal-like than low- or intermediate-grade lesions. Among invasive tumours, basal-like and HER2 type tumours were more likely to be more than 2 cm in size, high-grade and have nodal involvement compared with luminal A tumours. CONCLUSION: The major molecular phenotypes previously identified among invasive breast cancers were also identified among cases of DCIS. However, the prevalence of the luminal A, luminal B and HER2 phenotypes differed significantly between DCIS and invasive breast cancers.

Pitfalls of Frozen Section in Gynecological Pathology: A Case of Endometrial Tumor With Sex Cord-Like Elements.

Endometrial stromal tumor with sex cord-like elements (ESTSCLE) is a rare entity that shares similar histological features with uterine tumors resembling ovarian sex cord tumors (UTROSCT). Differentiating the 2 entities involves ample sampling of the tissue to distinguish the percentage of sex cord components within the tissue, genetic studies, and immunohistochemical staining. Frozen section provides limited information for exclusion of either tumor; and the tumor is rare enough that the diagnosis may not be considered with the limited sampling; therefore, deferral of diagnosis to permanent sections may be appropriate.

Fibrosis heterogeneity in nonalcoholic steatohepatitis and hepatitis C virus needle core biopsy specimens.

We examined 46 nonalcoholic steatohepatitis (NASH) and 52 hepatitis C virus (HCV) biopsy specimens to determine the magnitude of fibrosis heterogeneity and minimum length for accurate fibrosis staging. Three fibrosis scores were recorded: lowest regional, highest regional, and most common overall. Mean specimen lengths were 1.6 and 1.8 cm in NASH and HCV, respectively (P = .283). Mean (highest minus lowest) fibrosis heterogeneity scores (highest regional fibrosis - lowest regional fibrosis) were 3.7 and 2.0 in NASH and HCV, respectively (P < .001). Of 36 NASH specimens longer than 1.0 cm, 31 (86%) had the highest regional fibrosis in the deepest sampled parenchyma. Shorter specimens were associated significantly with greater fibrosis heterogeneity in NASH (coefficient, -1.3; P < .001) but not in HCV (P = .901). NASH specimens longer than 1.6 cm had significantly lower mean heterogeneity scores than specimens 1.6 cm or shorter (1.2 vs 3.4; P = .012). In NASH, fibrosis heterogeneity can be substantial and is greater than in HCV, and parenchymal injury, fibrosis, and healing might vary in different regions of the liver. The fibrosis stage in patients with NASH might not be assessed accurately in short specimens. Individual needle cores should be longer than 1.6 cm in NASH for accurate fibrosis staging.

Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis.

BACKGROUND: DNA-based HFE gene testing can confirm hereditary hemochromatosis in most people of Northern European descent. However, liver biopsy is important to detect cirrhosis. OBJECTIVE: To develop noninvasive criteria to predict the presence or absence of advanced hepatic fibrosis or cirrhosis in Americans with hemochromatosis. DESIGN: Cross-sectional study. SETTING: Six tertiary care referral clinics. PATIENTS: 182 patients with phenotypically defined hemochromatosis. MEASUREMENTS: Liver histopathology and serum ferritin, aspartate aminotransferase, and alanine aminotransferase levels. Multivariate logistic regression analysis was used to examine factors associated with cirrhosis (defined as bridging fibrosis or unequivocal cirrhosis on biopsy). RESULTS: Cirrhosis was present in 40 of 182 (22%) patients in the overall group and in 35 of 147 (24%) of C282Y homozygotes. Only 1 of 93 patients with a serum ferritin level less than 1000 microg/L had cirrhosis compared with 39 of 89 patients with serum ferritin levels greater than 1000 microg/L (P < 0.001). No C282Y homozygotes or C282Y/H63D compound heterozygotes with serum ferritin levels less than 1000 microg/L had cirrhosis. Elevated serum aminotransferase levels (P = 0.001) and serum ferritin levels greater than 1000 microg/L (P = 0.001), but not age older than 40 years (P = 0.2), were independently associated with cirrhosis. In a multivariate model, the probability of cirrhosis was 7.4% among patients with serum ferritin levels less than 1000 microg/L compared with 72% among patients with serum ferritin levels greater than 1000 microg/L after adjustment for age and elevated serum liver enzyme levels. CONCLUSIONS: Patients with hemochromatosis and serum ferritin levels less than 1000 microg/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels.